Temporal analysis of enhancers during mouse cerebellar development reveals dynamic and novel regulatory functions DOI Creative Commons
Miguel Ramirez, Yuliya Badayeva, Joanna Yeung

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 9, 2022

We have identified active enhancers in the mouse cerebellum at embryonic and postnatal stages which provides a view of novel during cerebellar development. The majority dynamic activity between Cerebellar were enriched for neural transcription factor binding sites with temporally specific expression. Putative gene targets displayed spatially restricted expression patterns, indicating cell-type regulation. Functional analysis target genes indicated that regulate processes spanning several developmental epochs such as specification, differentiation maturation. use these analyses to discover one regulator marker development: Bhlhe22 Pax3, respectively. an enrichment de novo mutations variants associated autism spectrum disorder enhancers. Furthermore, by comparing our data relevant brain development ENCODE histone profiles single-cell datasets we been able generalize expand on presented analyses, made results available online Developing Mouse Cerebellum Enhancer Atlas , where dataset can be efficiently queried, curated exported scientific community facilitate future research efforts. Our study valuable resource studying dynamics regulation developing delivers rich gene-enhancer associations providing basis in-depth studies cerebellum.

Language: Английский

Detecting signatures of selection on gene expression DOI
Peter D. Price, Daniela H. Palmer Droguett, Jessica A. Taylor

et al.

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(7), P. 1035 - 1045

Published: May 12, 2022

Language: Английский

Citations

75
Molecular diversity and evolution of neuron types in the amniote brain DOI
David Hain, Tatiana Gallego‐Flores,

Michaela Klinkmann

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6610)

Published: Sept. 1, 2022

The existence of evolutionarily conserved regions in the vertebrate brain is well established. rules and constraints underlying evolution neuron types, however, remain poorly understood. To compare types across species, we generated a cell type atlas bearded dragon compared it with mouse datasets. Conserved classes neurons could be identified from expression hundreds genes, including homeodomain-type transcription factors genes involved connectivity. Within these classes, there are both divergent precluding simple categorization into ancestral novel areas. In thalamus, neuronal diversification correlates cortex, suggesting that developmental origin circuit allocation drivers identity evolution.

Language: Английский

Citations

75
Cellular development and evolution of the mammalian cerebellum DOI Creative Commons
Mari Sepp, Kevin Leiss, Florent Murat

et al.

Nature, Journal Year: 2023, Volume and Issue: 625(7996), P. 788 - 796

Published: Nov. 29, 2023

The expansion of the neocortex, a hallmark mammalian evolution

Language: Английский

Citations

65
Conserved and divergent gene regulatory programs of the mammalian neocortex DOI Creative Commons
Nathan R. Zemke, Ethan J. Armand, Wenliang Wang

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 390 - 402

Published: Dec. 13, 2023

Abstract Divergence of cis- regulatory elements drives species-specific traits 1 , but how this manifests in the evolution neocortex at molecular and cellular level remains unclear. Here we investigated gene programs primary motor cortex human, macaque, marmoset mouse using single-cell multiomics assays, generating expression, chromatin accessibility, DNA methylome chromosomal conformation profiles from a total over 200,000 cells. From these data, show evidence that divergence transcription factor expression corresponds to epigenome landscapes. We find conserved divergent features are reflected three-dimensional genome. Transposable contribute nearly 80% human-specific candidate cortical Through machine learning, develop sequence-based predictors different species demonstrate genomic syntax is highly preserved rodents primates. Finally, epigenetic conservation combined with sequence similarity helps uncover functional enhances our ability interpret genetic variants contributing neurological disease traits.

Language: Английский

Citations

46
Developmental origins and evolution of pallial cell types and structures in birds DOI
Bastienne Zaremba, Amir Fallahshahroudi, Céline Schneider

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6735)

Published: Jan. 2, 2025

Innovations in the pallium likely facilitated evolution of advanced cognitive abilities birds. We therefore scrutinized its cellular composition and using cell type atlases from chicken, mouse, nonavian reptiles. found that avian shares most inhibitory neuron types with other amniotes. Whereas excitatory amniote hippocampal regions show evolutionary conservation, those pallial have diverged. Neurons mesopallium display gene expression profiles akin to mammalian claustrum deep cortical layers, while certain nidopallial resemble neurons piriform cortex. Lastly, we observed substantial convergence between dorsally located hyperpallium ventrally nidopallium during late development, suggesting topological location does not always dictate programs determining functional properties adult pallium.

Language: Английский

Citations

3
Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus DOI Creative Commons
Yi‐Cheng Wu,

Vladyslav I. Korobeynyk,

Margherita Zamboni

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: 28(2), P. 415 - 430

Published: Jan. 6, 2025

Abstract The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, DG dysfunction has been implicated age-related diseases. Although neurogenic potential maintained throughout life the as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, implications for cognitive decline disease. In this study, we used single-cell RNA sequencing characterize transcriptomic signatures their surrounding niche, identifying molecular changes associated aging from activation quiescent NSCs maturation fate-committed progeny. By integrating spatial transcriptomics data, identified regional invasion inflammatory into hippocampus age show here that early-onset neuroinflammation activity. Our data reveal lifelong dynamics niche provide a powerful resource understand alterations hippocampus.

Language: Английский

Citations

2
Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina DOI Creative Commons
Pin Lyu, Thanh Hoang, Clayton P. Santiago

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 37(7), P. 109994 - 109994

Published: Nov. 1, 2021

Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA ATAC sequencing (scATAC-seq) analysis mouse human retina to identify multiple interconnected, evolutionarily conserved GRNs composed cell-type-specific that both activate genes within own network inhibit other networks. These temporal patterning primary progenitors, regulate transition from neurogenic drive each major retinal cell type. We confirm NFI selectively expression promoting late-stage identity progenitors rod photoreceptor postnatal retina. This study inventories cis- trans-acting development can guide cell-based therapies aimed at replacing neurons lost disease.

Language: Английский

Citations

101
SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks DOI Open Access
Carmen Bravo González‐Blas, Seppe De Winter, Gert Hulselmans

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 19, 2022

Joint profiling of chromatin accessibility and gene expression individual cells provides an opportunity to decipher enhancer-driven regulatory networks (eGRN). Here we present a new method for the inference eGRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TF) links these target genes. Specific TFs each cell type or state are predicted based on concordance TF binding site accessibility, expression, expression. To improve both recall precision identification, curated clustered more than 40,000 position weight matrices that could associate 1,553 human TFs. We validated benchmarked components diverse data sets from different species, including peripheral blood mononuclear types, ENCODE lines, melanoma states, Drosophila retinal development. Next, exploit predictions study conserved TFs, enhancers, GRNs between mouse types in cerebral cortex. Finally, provide capabilities inferred eGRNs dynamics regulation differentiation trajectories; map activities onto tissues using spatial omics data; predict effect perturbations state. critical insight into regulation, starting multiome atlases scATAC-seq scRNA-seq. The suite is available as set Python modules at https://scenicplus.readthedocs.io .

Language: Английский

Citations

61
Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders DOI Open Access
Parthiv Haldipur, Kathleen J. Millen, Kimberly A. Aldinger

et al.

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 515 - 531

Published: April 20, 2022

Developmental abnormalities of the cerebellum are among most recognized structural brain malformations in human prenatal imaging. Yet reliable information regarding their cause humans is sparse, and few outcome studies available to inform prognosis. We know very little about cerebellar development, stark contrast wealth knowledge from decades research on developmental biology model organisms, especially mice. Recent show that multiple aspects development significantly differ mice even rhesus macaques, a nonhuman primate. These discoveries challenge many current mouse-centric models normal pathogenesis several neurodevelopmental phenotypes affecting cerebellum, including Dandy-Walker malformation medulloblastoma. Since we cannot what do not know, additional normative pathological data essential, new needed.

Language: Английский

Citations

43
Lifelong restructuring of 3D genome architecture in cerebellar granule cells DOI
Longzhi Tan, Jenny Shi, Siavash Moghadami

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6662), P. 1112 - 1119

Published: Sept. 7, 2023

The cerebellum contains most of the neurons in human brain and exhibits distinctive modes development aging. In this work, by developing our single-cell three-dimensional (3D) genome assay—diploid chromosome conformation capture, or Dip-C—into population-scale (Pop-C) virus-enriched (vDip-C) modes, we resolved first 3D structures single cerebellar cells, created life-spanning atlases for both humans mice, jointly measured transcriptome chromatin accessibility during development. We found that although granule mature early postnatal life, architecture gradually remodels throughout establishing ultra–long-range intrachromosomal contacts specific interchromosomal are rarely seen neurons. These results reveal unexpected evolutionarily conserved molecular processes underlie features neural aging across mammalian life span.

Language: Английский

Citations

42